Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation
Authors: Sara Lonardi, Cosimo Rasola, Riccardo Lobefaro, Daniele Rossini, Vincenzo Formica, Mario Scartozzi, Giovanni Luca Frassineti, Giorgia Boscolo, Saverio Cinieri, Samantha Di Donato, Nicoletta Pella, Francesca Bergamo, Alessandra Raimondi, Ermenegildo Arnoldi, Lorenzo Antonuzzo, Cristina Granetto, Fable Zustovich, Monica Ronzoni, Silvana Leo, Federica Morano, Fotios Loupakis, Federica Buggin, Vittorina Zagonel, Matteo Fassan, Chiara Cremolini, Luca Boni, Filippo Pietrantonio, Ermenegildo Arnoldi, Lorenzo Antonuzzo, Giuseppe Aprile, Antonio Ardizzoia, Carlo Aschele, Editta Baldini, Alberto Ballestrero, Alessandro Bertolini, Roberto Bordonaro, Giorgia Boscolo, Angela Buonadonna, Saverio Cinieri, Matteo Clavarezza, Domenico Corsi, Enrico Cortesi, Filippo De Braud, Samantha Di Donato, Alfredo Falcone, Adolfo Favaretto, Vincenzo Formica, Luca Frassineti, Antonio Frassoldati, Michela Frisinghelli, Teresa Gamucci, Luca Gianni, Filippo Giovanardi, Stefania Gori, Roberta Grande, Cristina Granetto, Silvana Leo, Francesco Leone, Sara Lonardi, Andrea Luciani, Carlo Milandri, Nicoletta Pella, Andrea Sartore-Bianchi, Mario Scartozzi, Nicola Silvestris, Emiliano Tamburini, Gianluca Tomasello, Giuseppe Tonini, Gianpaolo Tortora, Claudio Vergani, Albrto Zaniboni, Fable Zustovich
Journal: Journal of Clinical Oncology (2023)

To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable RAS/BRAF wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time ≤6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (P < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with RAS/BRAF wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.